Recruiting
Phase 2

Lutetium Lu 177 Dotatate

Sponsor:

National Cancer Institute (NCI)

Code:

NCT04665739

Conditions

Advanced Lung Neuroendocrine Tumor

Functioning Lung Neuroendocrine Tumor

Locally Advanced Lung Neuroendocrine Neoplasm

Lung Neuroendocrine Neoplasm

Lung Neuroendocrine Tumor G1

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Computed Tomography

Everolimus

Fludeoxyglucose F-18

Lutetium Lu 177 Dotatate

Study Details

Brief summary:

This phase II trial studies the effect of lutetium Lu 177 dotatate compared to the usual treatment (everolimus) in treating patients with somatostatin receptor positive bronchial neuroendocrine tumors that have spread to other places in the body (advanced). Lutetium Lu 177-dotate is a radioactive drug. It binds to a protein called somatostatin receptor, which is found on some neuroendocrine tumor cells. Lutetium Lu 177-dotatate builds up in these cells and gives off radiation that may kill them. It is a type of radioconjugate and a type of somatostatin analog. Lutetium Lu 177 dotatate may be more effective than everolimus in shrinking or stabilizing advanced bronchial neuroendocrine tumors.

Conditions

Advanced Lung Neuroendocrine Tumor

Functioning Lung Neuroendocrine Tumor

Locally Advanced Lung Neuroendocrine Neoplasm

Lung Neuroendocrine Neoplasm

Lung Neuroendocrine Tumor G1

Study ID

NCT04665739

Start date

Feb 3, 2023

Status verified date

Apr, 2026

Completion date

Jul 1, 2027

Anticipated

Primary completion date

Jul 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • PRE-REGISTRATION: Pathologic Documentation: Well- or moderately-differentiated neuroendocrine tumor(s) of bronchial origin (i.e. carcinoid) as assessed by local pathology

  • The pathology report must state ONE of the following:

  • Well- or moderately-differentiated neuroendocrine tumor,
  • Low- or intermediate-grade neuroendocrine tumor, or
  • Carcinoid tumor (including typical or atypical carcinoid tumors)
  • PRE-REGISTRATION: Documentation of histology from a primary or metastatic site is allowed
  • PRE-REGISTRATION: Functional (evidence of peptide hormones and/or bioactive substances associated with a clinical hormone syndrome such as carcinoid syndrome or Cushing's syndrome) or nonfunctional tumors are allowed
  • PRE-REGISTRATION: Patients with poorly-differentiated or high-grade neuroendocrine carcinoma (i.e. large cell neuroendocrine carcinoma of lung, small cell lung cancer) or mixed tumors (i.e. adenocarcinoid tumor) are not eligible
  • PRE-REGISTRATION: Recurrent or locally-advanced/unresectable or metastatic disease
  • PRE-REGISTRATION: Neuroendocrine tumor of bronchial (i.e. lung) primary site
  • PRE-REGISTRATION: Lesions must have shown radiological evidence of disease progression in the 12 months prior to pre-registration

  • Tumor must have shown somatostatin receptor (SSTR) positivity on 68Ga-DOTATATE PET or other SSTR-PET scan in the 12 months prior to pre-registration; however, documentation of SSTR positivity in the 6 months prior to pre-registration is preferred. SSTR positivity is defined as uptake greater than background liver in all measurable lesions
  • PRE-REGISTRATION: Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 by computer tomography (CT) scan or magnetic imaging (MRI). Any lesions which have undergone percutaneous therapies or radiotherapy should not be considered measurable unless the lesion has clearly progressed since the procedure
  • PRE-REGISTRATION: Lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as >= 1 cm with CT or MRI (or >= 1.5 cm short axis for lymph nodes). Non-measurable disease includes disease smaller than these dimensions or lesions considered truly non-measurable including: leptomeningeal disease, bone metastases, ascites, pleural or pericardial effusion, lymphangitic involvement of skin or lung
  • REGISTRATION: Confirmation of SSTR positivity by Alliance Imaging Core Lab (ICL) at Imaging and Radiation Oncology Core (IROC) Ohio central radiographic review
  • REGISTRATION: Patients with treatment-naive or previously-treated disease are allowed. Patients with previously-treated disease must have demonstrated radiographic disease progression on the prior therapy
  • REGISTRATION: No prior treatment with peptide receptor radionuclide therapy (PRRT) (e.g. lutetium Lu 177 dotatate)
  • REGISTRATION: No prior treatment with mammalian target of rapamycin (mTOR) inhibitors (e.g. deforolimus, everolimus, sirolimus, temsirolimus, etc.)
  • REGISTRATION: Prior treatment with hepatic artery embolization (including bland embolization, chemoembolization, and selective radioembolization) or ablative therapies (i.e. cryoablation, radiofrequency ablation, etc.) is allowed if measurable disease remains outside of the treated area or if there is documented disease progression in a treated site. Prior liver-directed (including ablative) treatment must be completed at least 28 days prior to registration
  • REGISTRATION: Prior treatment with 90-Yttrium radioembolization must be completed at least 6-weeks prior to registration
  • REGISTRATION: Radiation therapy to the lung and/or mediastinum must be completed at least 14 days prior to registration for stereotactic ablative and at least 28 days prior to registration for conventional fractionation
  • REGISTRATION: Prior treatment with systemic anticancer therapy must be completed at least 28 days prior to registration (except for somatostatin analogs in patients with functional tumors). Continuation of treatment with somatostatin analogs while on protocol therapy is allowed provided that the patient:

  • Has functional tumors (evidence of peptide hormones and/or bioactive substances associated with a clinical hormone syndrome such as carcinoid syndrome or Cushing's syndrome), and
  • Has previously demonstrated radiographic disease progression while on somatostatin analog therapy
  • REGISTRATION: Patients must have completed any major surgery at least 28 days prior to registration. Complete wound healing from major surgery should occur prior to registration
  • REGISTRATION: Patients should have improvement of any toxic effects of prior therapy (except alopecia, fatigue, and other non-reversible toxic effects such as neuropathy from cisplatin) to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, grade 1 or less
  • REGISTRATION: Not pregnant and not nursing

  • Therefore, for women of childbearing potential only, a negative pregnancy test done =< 28 days prior to registration is required
  • REGISTRATION: Age >= 18 years
  • REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • REGISTRATION: Hemoglobin >= 8.0 g/dL
  • REGISTRATION: Platelet count >= 75,000/mm\^3
  • REGISTRATION: Absolute neutrophil count (ANC) >= 1,500/mm\^3
  • REGISTRATION: Creatinine =< 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance >= 40 mL/min

  • Calculated by the Cockcroft-Gault equation
  • REGISTRATION: Total bilirubin =< 2.0 x ULN

  • In patients with Gilbert's syndrome, if total bilirubin is > 2.0 x ULN, then direct bilirubin must be =< 2.0 x ULN
  • REGISTRATION: Albumin >= 2.8 g/dL
  • REGISTRATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x ULN
  • REGISTRATION: No known central nervous system metastases unless treated and clinically stable for at least 14 days prior to registration. Patients on steroid support must be clinically stable on weaning doses of steroids
  • REGISTRATION: No other currently active malignancy that requires therapy or is expected to require therapy during the study (excluding non-melanoma skin cancers or in situ carcinomas, such as breast or cervical)
  • REGISTRATION: No known active hepatitis B (defined as hepatitis B surface antigen \[HbsAg\] reactive) or known active hepatitis C virus (defined as hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] viral load detected). The exception is for patients with known active hepatitis B virus (defined as HbsAg reactive) infection, where the HBV viral load must be undetectable on suppressive therapy for patient to be eligible
  • REGISTRATION: Patients with known human immunodeficiency virus (HIV) infections on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial
  • REGISTRATION: No known active or uncontrolled infections requiring ongoing antifungals or antibiotics in the 3 days prior to registration
  • REGISTRATION: No receipt of live attenuated vaccines in the 7 days prior to registration
  • REGISTRATION: No known decompensated liver cirrhosis
  • REGISTRATION: No known prior drug-induced pneumonitis that was symptomatic or required treatment
  • REGISTRATION: No known medical condition causing an inability to swallow and no known impairment of gastrointestinal function that may significantly alter the absorption of an oral agent
  • REGISTRATION: No known hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus, etc.)
  • REGISTRATION: Concurrent somatostatin analog use while on protocol therapy is allowed provided that the patient: 1) has a functional tumor (evidence of peptide hormones and/or bioactive substances associated with a clinical hormone syndrome such as carcinoid syndrome or Cushing's syndrome), 2) has previously demonstrated radiographic disease progression while on somatostatin analog therapy
  • REGISTRATION: Chronic concomitant treatment with P-gp and strong CYP3A4 inhibitors and/or inducers is not allowed on the everolimus treatment arm of this study. Given that the study is randomized, all patients on P-gp and strong CYP3A4 inhibitors and/or inducers must discontinue the drug(s) 7 days prior to registration
  • RE-REGISTRATION: Confirmation of disease progression by RECIST v1.1 by real-time Alliance ICL at IROC Ohio central radiographic review
  • RE-REGISTRATION: Not pregnant and not nursing

  • Women of childbearing potential only, a negative pregnancy test done =< 28 days prior to re-registration is required
  • RE-REGISTRATION: ECOG performance status 0-2
  • RE-REGISTRATION: Hemoglobin >= 8.0 g/dL
  • RE-REGISTRATION: Platelet count >= 75,000/mm\^3
  • RE-REGISTRATION: Absolute neutrophil count (ANC) >= 1,500/mm\^3
  • RE-REGISTRATION: Creatinine =< 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance >= 40 mL/min

  • Calculated by the Cockcroft-Gault equation
  • RE-REGISTRATION: Total bilirubin =< 2.0 x ULN

  • In patients with Gilbert's syndrome, if total bilirubin is > 2.0 x ULN, then direct bilirubin must be =< 2.0 x ULN
  • RE-REGISTRATION: Albumin >= 2.8 g/dL
  • RE-REGISTRATION: AST/ALT =< 3.0 x ULN

Study Design

Enrollment

70 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm I (lutetium Lu 177 dotatate)

Patients receive lutetium Lu 177 dotatate IV over 30-40 minutes on day 1 of each cycle. Treatment repeats every 56 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET during screening. Patients also undergo CT or MRI during screening and on the trial as well as FDG PET and SPECT on the trial. Additionally, patients undergo blood and tissue sample collection during screening and on the trial.

active comparator: Arm II (everolimus)

Patients receive everolimus PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may be able to cross-over to Arm I. Patients undergo PET during screening. Patients also undergo CT or MRI during screening and on the trial as well as FDG PET and SPECT on the trial. Additionally, patients undergo blood and tissue sample collection during screening and on the trial.

Interventions

Biospecimen Collection

Undergo blood and tissue sample collection

Computed Tomography

Undergo CT

Everolimus

Given PO

Fludeoxyglucose F-18

Given FDG

Lutetium Lu 177 Dotatate

Given IV

Magnetic Resonance Imaging

Undergo MRI

Positron Emission Tomography

Undergo PET

Single Photon Emission Computed Tomography

Undergo SPECT

Survey Administration

Ancillary studies

Primary outcome measure

  • Median progression-free survival (PFS) [ Time Frame: From randomization until either radiographic progression confirmed by central radiology review or death, assessed up to 5 years from study registration ]

Central Contacts and Locations

Locations

Tower Cancer Research Foundation

Recruiting

Beverly Hills, California, United States, 90211

Contacts

Site Public Contact

towercancerresearch@toweroncology.com

Principal Investigator:

Andrew E. Hendifar

Cedars-Sinai Medical Center

Recruiting

Los Angeles, California, United States, 90048

Contacts

Site Public Contact

310-423-2133Cancer.trial.info@cshs.org

Principal Investigator:

Andrew E. Hendifar

Torrance Memorial Physician Network - Cancer Care

Recruiting

Torrance, California, United States, 90505

Contacts

Site Public Contact

310-750-3300courtney.steeneken@tmphysicians.com

Principal Investigator:

Andrew E. Hendifar

UM Sylvester Comprehensive Cancer Center at Coral Gables

Recruiting

Coral Gables, Florida, United States, 33146

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Lawrence M. Negret

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Recruiting

Deerfield Beach, Florida, United States, 33442

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Lawrence M. Negret

University of Miami Miller School of Medicine-Sylvester Cancer Center

Recruiting

Miami, Florida, United States, 33136

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Lawrence M. Negret

UM Sylvester Comprehensive Cancer Center at Plantation

Recruiting

Plantation, Florida, United States, 33324

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Lawrence M. Negret

University of Chicago Comprehensive Cancer Center

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Site Public Contact

773-702-8222cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Christine M. Bestvina

UC Comprehensive Cancer Center at Silver Cross

Recruiting

New Lenox, Illinois, United States, 60451

Contacts

Site Public Contact

773-702-8222cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Christine M. Bestvina

University of Chicago Medicine-Orland Park

Recruiting

Orland Park, Illinois, United States, 60462

Contacts

Site Public Contact

773-702-8222cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Christine M. Bestvina

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Recruiting

Ankeny, Iowa, United States, 50023

Contacts

Site Public Contact

515-241-3305

Principal Investigator:

Seema Harichand-Herdt

Iowa Methodist Medical Center

Recruiting

Des Moines, Iowa, United States, 50309

Contacts

Site Public Contact

515-241-6727

Principal Investigator:

Seema Harichand-Herdt

UI Health Care Mission Cancer and Blood - Des Moines Clinic

Recruiting

Des Moines, Iowa, United States, 50309

Contacts

Site Public Contact

515-241-3305

Principal Investigator:

Seema Harichand-Herdt

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Site Public Contact

877-442-3324

Principal Investigator:

Jennifer A. Chan

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Site Public Contact

855-776-0015

Principal Investigator:

Thorvardur R. Halfdanarson

Missouri Baptist Medical Center

Recruiting

St Louis, Missouri, United States, 63131

Contacts

Site Public Contact

314-996-5569

Principal Investigator:

Bryan A. Faller

Case Western Reserve University

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

Site Public Contact

800-641-2422CTUReferral@UHhospitals.org

Principal Investigator:

Amr Mohamed

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Site Public Contact

800-293-5066Jamesline@osumc.edu

Principal Investigator:

Vineeth Sukrithan

Fox Chase Cancer Center

Recruiting

Philadelphia, Pennsylvania, United States, 19111

Contacts

Site Public Contact

215-728-4790

Principal Investigator:

Sukhmani K. Padda

Temple University Hospital

Recruiting

Philadelphia, Pennsylvania, United States, 19140

Contacts

Site Public Contact

215-728-2983

Principal Investigator:

Sukhmani K. Padda

UPMC Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contacts

Site Public Contact

412-647-8073

Principal Investigator:

Liza C. Villaruz

Vanderbilt University/Ingram Cancer Center

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

Site Public Contact

800-811-8480

Principal Investigator:

Robert A. Ramirez

Huntsman Cancer Institute/University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

Contacts

Site Public Contact

888-424-2100cancerinfo@hci.utah.edu

Principal Investigator:

Heloisa P. Soares

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Aug 20, 2026

Last verified

Apr, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-08-20.